Chronic ethanol consumption and senescence are both known to cause memory deficits and to cause similar morphdogical changes in the hippocampus, a brain region associated with memory. In Addition, both ethanol and senescence alter cholinergic neurotransmission, a process implicated in the cognitive processes which decline during normal aging and in chronic alcoholics. Recently, we have shown that chronic ethanol administration increases the cholesterol to phospholipid molar ratio in synaptosomal membranes. In a separate series of experiments we found that the cholesterol to phospholipid ratio of synaptosomal membranes increases as rats approach senescence. This change in membrane composition alters membrane properties and neurotransmission. Acetylcholine is known to be a potent stimulant of hippocampal pyramidal cell firing and to increase phospholipid metabolism. We have recently developed a technique to reversibly increase the relative cholesterol content of hippocampal brain slices. An increased in the relative cholesterol content markedly reduces the response to acetylcholine. Furthermore, iontophoretic as well as hippocampal slice studies have shown that the hippocampal response to acetylcholine declines in senesent rats. Thus, we hypothesize that changes in membrane composition which occur during chronic ethanol consumption and aging can reduce the response of hippocampal pyramidal cells to acetylcholine and thereby may cause memory dysfunction. Using hippocampal slices prepared from young and old Fisher 344 rats we propose to determine the relationship between the alterations in membranes which occur during chronic ethanol consumption and the electrophysiological and phospholipid metabolism responses to acetylcholine. The changes which occur during chronic ethanol treatment of both young and old rats will be studied as well as the effects of in-vitro modification of membrane lipids on the responses to acetylcholine and ethanol). In addition, the effects of in-vitro ethanol on membrane properties will be compared to the effects of in-vitro ethanol on the responses to acethylcholine in hippocampal slices. These studies will provide insight into the pathological mechanisms of chronic ethanol consumption; the interaction between ethanol and aging, as well as the susceptability of old animals to the pathological actions of ethanol.